The goal of this project is to understand at both the molecular and organismal levels how internal organs arise during vertebrate embryogenesis, in particular the developmental origins of the circulatory system. We wish to examine how vascular progenitors (angioblasts) and are specified, how vascular patterning and morphogenesis is regulated, and how the differentiation of functionally distinct vascular beds is accomplished. We use the zebrafish, a vertebrate well suited for studying the early development of the vasculature because of its genetic tractability, and the accessibility and optical clarity of its embryos. Our current research is directed at (1) uncovering novel circulatory system-specific genes, (2) determining the etiology and molecular basis for a number of circulatory system-specific mutations, and (3) deriving a detailed descriptive understanding of the ontogeny, patterning, and morphogenesis of embryonic circulatory tissues.We are studying three zebrafish mutations that cause specific regional defects in vascular patterning, some of which resemble human congenital cardiovascular defects. The first mutation causes a defect in cranial angiogenesis, the second results in formation of an arterial-venous shunt from the aortic arches, and a third causes a localized defect in the dorsal aorta. Efforts are underway to determine the molecular basis for all three of these mutants and further probe the nature of their phenotypic defects. We are also working to understand the basis for trunk axial vessel formation, particularly how local cues guide assembly of the adjacent dorsal aorta (DA) and posterior cardinal vein (PCV) and how their arterial-venous identity is established. We have obtained evidence supporting a two-signal model for trunk axial vessel formation reminiscent of that invoked to explain the dorsoventral patterning of the neural tube. Endoderm and hypochord provide reciprocal and synergistic cues for formation of the PCV and DA, respectively. We are currently exploring the nature of these cues at the molecular level. - zebrafish,circulatory system,blood vessels,blood cells,gridlock,arteries,veins,hematopoiesis,vascular endothelium